Dexmedetomidine increases acetylation level of histone through ERK1/2 pathway in dopamine neuron
Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedation, anesthetic sparing, analgesia, sympatholytic, and neuroprotective properties. This study evaluated neuroprotective effects of dexmedetomidine on dopamine neurons correlated to histone acetylation via extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) pathway. Animals were randomly assigned to four groups and treatments were given as onetime doses: dimethyl sulfoxide (DMSO; n = 6), dexmedetomidine 1 mg/kg (n = 6), 10 mg/kg (n = 6), and 100 mg/kg (n = 6). Acetylation histone protein levels and ERK protein levels in rats dopamine neuron from striatum were determined by Western blotting after various doses of dexmedetomidine (1, 10, and 100 mg/kg) treatments. The messenger RNA expression related to signal transduction coupled to 5-hydroxytryptamine receptor (5-HTR) in striatum was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Dexmedetomidine administration increased expression of ERK1/2 phosphorylation and histones H3 acetylation. PD098059, an inhibitor of pERK1/2, almost completely blocked dexmedetomidine-induced histones H3 acetylation. In addition, bioinformatics analysis in combination with qRT-PCR demonstrated that dexmedetomidine could regulate the genes that are related to signal transduction coupled to 5-HTR via α2-adrenoceptor. Our results define dexmedetomidine as a modulator of histones H3 acetylation via ERK1/2 signaling pathway in dopamine neuron from striatum, which may provide clues for the mechanism underlying the neuroprotective effects of dexmedetomidine..
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2017 |
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| Erschienen: |
2017 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:36 |
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| Enthalten in: |
Human & experimental toxicology - 36(2017), 5, Seite 474-482 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hu, S-P [VerfasserIn] |
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| Links: |
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| doi: |
10.1177/0960327116652458 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Dexmedetomidine is a highly selective α2-adrenoceptor agonist with sedation, anesthetic sparing, analgesia, sympatholytic, and neuroprotective properties. This study evaluated neuroprotective effects of dexmedetomidine on dopamine neurons correlated to histone acetylation via extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) pathway. Animals were randomly assigned to four groups and treatments were given as onetime doses: dimethyl sulfoxide (DMSO; n = 6), dexmedetomidine 1 mg/kg (n = 6), 10 mg/kg (n = 6), and 100 mg/kg (n = 6). Acetylation histone protein levels and ERK protein levels in rats dopamine neuron from striatum were determined by Western blotting after various doses of dexmedetomidine (1, 10, and 100 mg/kg) treatments. The messenger RNA expression related to signal transduction coupled to 5-hydroxytryptamine receptor (5-HTR) in striatum was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) analysis. Dexmedetomidine administration increased expression of ERK1/2 phosphorylation and histones H3 acetylation. PD098059, an inhibitor of pERK1/2, almost completely blocked dexmedetomidine-induced histones H3 acetylation. In addition, bioinformatics analysis in combination with qRT-PCR demonstrated that dexmedetomidine could regulate the genes that are related to signal transduction coupled to 5-HTR via α2-adrenoceptor. Our results define dexmedetomidine as a modulator of histones H3 acetylation via ERK1/2 signaling pathway in dopamine neuron from striatum, which may provide clues for the mechanism underlying the neuroprotective effects of dexmedetomidine. | ||
| 540 | |a Nutzungsrecht: © The Author(s) 2016 | ||
| 650 | 4 | |a Animals | |
| 650 | 4 | |a Sulphoxides | |
| 650 | 4 | |a Histones | |
| 650 | 4 | |a Neuroprotection | |
| 650 | 4 | |a Correlation analysis | |
| 650 | 4 | |a Dimethyl | |
| 650 | 4 | |a Gene expression | |
| 650 | 4 | |a Kinases | |
| 650 | 4 | |a Rats | |
| 650 | 4 | |a Extracellular signal-regulated kinase | |
| 650 | 4 | |a Analgesia | |
| 650 | 4 | |a Dopamine | |
| 650 | 4 | |a Phosphorylation | |
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| 650 | 4 | |a Polymerase chain reaction | |
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| 650 | 4 | |a Studies | |
| 650 | 4 | |a Serotonin | |
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| 650 | 4 | |a Acetylation | |
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| 650 | 4 | |a Adrenergic receptors | |
| 650 | 4 | |a Bioinformatics | |
| 650 | 4 | |a Transduction | |
| 650 | 4 | |a Signal transduction | |
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| 700 | 1 | |a Wang, W-X |4 oth | |
| 700 | 1 | |a Liu, Y |4 oth | |
| 700 | 1 | |a Wu, H-F |4 oth | |
| 700 | 1 | |a Chen, C |4 oth | |
| 700 | 1 | |a Yu, L |4 oth | |
| 700 | 1 | |a Gui, J-B |4 oth | |
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